Clinical features, outcomes, and long-term survival times of cats and dogs with central nervous system cryptococcosis in Australia: 50 cases (2000–2020)

Else Jacobson Department of Internal Medicine, Veterinary Specialist Services, Underwood, QLD, Australia

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 BVSc
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John M. Morton Jemora Pty Ltd, East Geelong, VIC, Australia

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 BVSc, PhD
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Dennis J. Woerde Department of Internal Medicine, Animal Referral Hospital, Homebush West, NSW, Australia

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Mary F. Thompson Department of Internal Medicine, The Animal Hospital, School of Veterinary Medicine, Murdoch University, Murdoch, WA, Australia

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 BVSc(Hons), PhD, DACVIM
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Amanda M. Spillane Department of Internal Medicine, Queensland Veterinary Specialists, Stafford, QLD, Australia

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Anna Tebb Department of Internal Medicine, Western Australian Veterinary Emergency and Specialty, Success, WA, Australia

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 MA, VetMB, MVM, DipECVIM-CA
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Zoe della Valle Department of Internal Medicine, Melbourne Veterinary Specialist Centre, Glen Waverley, VIC, Australia

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Gemma Birnie Department of Internal Medicine, Brisbane Veterinary Specialist Centre, Albany Creek, QLD, Australia

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Richard Malik Centre for Veterinary Education, Veterinary Science Conference Centre, The University of Sydney, NSW, Australia

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 DVSc, PhD, FACVSc

Abstract

OBJECTIVE

To describe the clinical findings and outcomes of Australian cats and dogs with CNS cryptococcosis.

ANIMALS

19 cats and 31 dogs with CNS cryptococcosis diagnosed between 2000 and 2020.

PROCEDURES

A case series and cohort study were performed using the same 50 animals. Both studies were multi-institutional and both retrospective and prospective. Disease features were compared between cats and dogs, and associations between putative risk factors and survival time (ST) were assessed.

RESULTS

Dogs were younger at initial presentation than cats and had lower latex cryptococcal antigen agglutination titers. Extraneurologic signs were common and frequently involved sinonasal and contiguous tissues. Neuroanatomic localization was predominantly forebrain, central vestibular (including cerebellum), multifocal, or diffuse. CSF analysis predominantly showed pleocytosis, with eosinophilic inflammation common in dogs. Seventy-eight percent (39/50) of patients received antifungal treatment. Median STs (from presentation) in treated patients were 1,678 days for cats and 679 days for dogs. Abnormal mentation at presentation (in dogs) and CSF collection (in cats) were associated with shorter STs. In treated dogs, those that received glucocorticoids prior to diagnosis, or single rather than multiple antifungal agents, had shorter STs.

CLINICAL RELEVANCE

The prognosis for feline and canine CNS cryptococcosis is guarded, yet long STs are possible with appropriate treatment. Presence of subtle upper respiratory tract signs may suggest cryptococcosis in patients with neurologic signs, while the absence of neurologic signs does not preclude CNS involvement.

Abstract

OBJECTIVE

To describe the clinical findings and outcomes of Australian cats and dogs with CNS cryptococcosis.

ANIMALS

19 cats and 31 dogs with CNS cryptococcosis diagnosed between 2000 and 2020.

PROCEDURES

A case series and cohort study were performed using the same 50 animals. Both studies were multi-institutional and both retrospective and prospective. Disease features were compared between cats and dogs, and associations between putative risk factors and survival time (ST) were assessed.

RESULTS

Dogs were younger at initial presentation than cats and had lower latex cryptococcal antigen agglutination titers. Extraneurologic signs were common and frequently involved sinonasal and contiguous tissues. Neuroanatomic localization was predominantly forebrain, central vestibular (including cerebellum), multifocal, or diffuse. CSF analysis predominantly showed pleocytosis, with eosinophilic inflammation common in dogs. Seventy-eight percent (39/50) of patients received antifungal treatment. Median STs (from presentation) in treated patients were 1,678 days for cats and 679 days for dogs. Abnormal mentation at presentation (in dogs) and CSF collection (in cats) were associated with shorter STs. In treated dogs, those that received glucocorticoids prior to diagnosis, or single rather than multiple antifungal agents, had shorter STs.

CLINICAL RELEVANCE

The prognosis for feline and canine CNS cryptococcosis is guarded, yet long STs are possible with appropriate treatment. Presence of subtle upper respiratory tract signs may suggest cryptococcosis in patients with neurologic signs, while the absence of neurologic signs does not preclude CNS involvement.

  • 1.

    McGill S, Malik R, Saul N, et al. Cryptococcosis in domestic animals in Western Australia: a retrospective study from 1995–2006. Med Mycol. 2009;47(6):625639. doi:10.1080/13693780802512519

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2.

    Sykes JE, Malik R. Cryptococcosis. In: Sykes JE, ed. Canine and Feline Infectious Diseases. WB Saunders; 2014:599612.

  • 3.

    Malik R, Wigney DI, Muir DB, Gregory DJ, Love DN. Cryptococcosis in cats: clinical and mycological assessment of 29 cases and evaluation of treatment using orally administered fluconazole. J Med Vet Mycol. 1992;30(2):133144. doi:10.1080/02681219280000181

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4.

    O’Brien CR, Krockenberger MB, Wigney DI, Martin P, Malik R. Retrospective study of feline and canine cryptococcosis in Australia from 1981 to 2001: 195 cases. Med Mycol. 2004;42(5):449460. doi:10.1080/13693780310001624547

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5.

    Trivedi SR, Sykes JE, Cannon MS, et al. Clinical features and epidemiology of cryptococcosis in cats and dogs in California: 93 cases (1988–2010). J Am Vet Med Assoc. 2011;239(3):357369. doi:10.2460/javma.239.3.357

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6.

    Vorathavorn VI, Sykes JE, Feldman DG. Cryptococcosis as an emerging systemic mycosis in dogs. J Vet Emerg Crit Care (San Antonio). 2013;23(5):489497. doi:10.1111/vec.12087

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7.

    Malik R, Dill-Macky E, Martin P, Wigney DI, Muir DB, Love DN. Cryptococcosis in dogs: a retrospective study of 20 consecutive cases. J Med Vet Mycol. 1995;33(5):291297. doi:10.1080/02681219580000601

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8.

    Sykes JE, Sturges BK, Cannon MS, et al. Clinical signs, imaging features, neuropathology, and outcome in cats and dogs with central nervous system cryptococcosis from California. J Vet Intern Med. 2010;24:14271438.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9.

    Lester SJ, Malik R, Bartlett KH, Duncan CG. Cryptococcosis: update and emergence of Cryptococcus gattii. Vet Clin Pathol. 2011;40(1):417. doi:10.1111/j.1939-165X.2010.00281.x

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10.

    Montoya MC, Magwene PM, Perfect JR. Associations between Cryptococcus genotypes, phenotypes, and clinical parameters of human disease: a review. J Fungi (Basel). 2021;7(4):260. doi:10.3390/jof7040260

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11.

    Chen SC-A, Meyer W, Sorrell TC. Cryptococcus gattii infections. Clin Microbiol Rev. 2014;27(4):9801024. doi:10.1128/CMR.00126-13

  • 12.

    Yang DH, England MR, Salvator H, et al. Cryptococcus gattii species complex as an opportunistic pathogen: underlying medical conditions associated with the infection. mBio. 2021;12(5):e0270821. doi:10.1128/mBio.02708-21

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13.

    Kerwin SC, McCarthy RJ, VanSteenhouse JL, et al. Cervical spinal cord compression caused by cryptococcosis in a dog: successful treatment with surgery and fluconazole. J Am Anim Hosp Assoc. 1998;34(6):523526. doi:10.5326/15473317-34-6-523

    • Search Google Scholar
    • Export Citation
  • 14.

    Tiches D, Vite CH, Dayrell-Hart B, Steinberg SA, Gross S, Lexa F. A case of canine central nervous system cryptococcosis: management with fluconazole. J Am Anim Hosp Assoc. 1998;34(2):145151. doi:10.5326/15473317-34-2-145

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15.

    Beatty JA, Barrs VR, Swinney GR, Martin PA, Malik R. Peripheral vestibular disease associated with cryptococcosis in three cats. J Feline Med Surg. 2000;2(1):2934. doi:10.1053/jfms.2000.0061

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16.

    Foster SF, Charles JA, Parker G, Krockenberger M, Churcher RM, Malik R. Cerebral cryptococcal granuloma in a cat. J Feline Med Surg. 2001;3(1):3944. doi:10.1053/jfms.2000.0112

    • Search Google Scholar
    • Export Citation
  • 17.

    Mellema LM, Samii VF, Vernau KM, LeCouteur RA. Meningeal enhancement on magnetic resonance imaging in 15 dogs and 3 cats. Vet Radiol Ultrasound. 2002;43(1):1015. doi:10.1111/j.1740-8261.2002.tb00435.x

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18.

    O’Toole TE, Sato AF, Rozanski EA. Cryptococcosis of the central nervous system in a dog (Erratum published in J Am Vet Med Assoc. 2003;223[5]:653). J Am Vet Med Assoc. 2003;222(12):17221725. doi:10.2460/javma.2003.222.1722

    • Search Google Scholar
    • Export Citation
  • 19.

    Belluco S, Thibaud JL, Guillot J, et al. Spinal cryptococcoma in an immunocompetent cat. J Comp Pathol. 2008;139(4):246251. doi:10.1016/j.jcpa.2008.06.007

    • Search Google Scholar
    • Export Citation
  • 20.

    Byrnes EJ III, Bildfell RJ, Dearing PL, Valentine BA, Heitman J. Cryptococcus gattii with bimorphic colony types in a dog in western Oregon: additional evidence for expansion of the Vancouver Island outbreak. J Vet Diagn Invest. 2009;21(1):133136. doi:10.1177/104063870902100122

    • Search Google Scholar
    • Export Citation
  • 21.

    Windsor RC, Sturges BK, Vernau KM, Vernau W. Cerebrospinal fluid eosinophilia in dogs. J Vet Intern Med. 2009;23(2):275281. doi:10.1111/j.1939-1676.2009.0276.x

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22.

    Hammond JJ, Glass EN, Bishop TM, Kent M, De Lahunta A. Imaging diagnosis-intracranial cryptococcal mass in a cat. Vet Radiol Ultrasound. 2011;52(3):306308. doi:10.1111/j.1740-8261.2011.01802.x

    • Search Google Scholar
    • Export Citation
  • 23.

    Headley SA, Mota FCD, Lindsay S, et al. Cryptococcus neoformans var. grubii-induced arthritis with encephalitic dissemination in a dog and review of published literature. Mycopathologia. 2016;181(7-8):595601. doi:10.1007/s11046-016-0009-4

    • Search Google Scholar
    • Export Citation
  • 24.

    Galban E, Perkins J. Arachnoid diverticulum diagnosis following treatment of cryptococcal meningitis in a dog. Clin Case Rep. 2018;6(4):557563. doi:10.1002/ccr3.1325

    • Search Google Scholar
    • Export Citation
  • 25.

    Barbry JB, Poinsard AS, Gomes E, Durand A, Balland O. Cryptococcosis with ocular and central nervous system involvement in a 3-year-old dog. Clin Case Rep. 2019;7(12):23492354. doi:10.1002/ccr3.2491

    • Search Google Scholar
    • Export Citation
  • 26.

    Berthelin C, Bailey C, Kass P. Cryptococcus of the nervous system in dogs, part 1: epidemiologic, clinical and neuropathologic features. Prog Vet Neurol. 1994;5:8897.

    • Search Google Scholar
    • Export Citation
  • 27.

    Berthelin C, Legendre A, Bailey C. Cryptococcosis of the nervous system in dogs, part 2: diagnosis, treatment, monitoring, and prognosis. Prog Vet Neurol. 1994;5:136146.

    • Search Google Scholar
    • Export Citation
  • 28.

    O’Brien CR, Krockenberger MB, Martin P, Wigney DI, Malik R. Long-term outcome of therapy for 59 cats and 11 dogs with cryptococcosis. Aust Vet J. 2006;84(11):384392. doi:10.1111/j.1751-0813.2006.00040.x

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29.

    Duncan C, Stephen C, Campbell J. Clinical characteristics and predictors of mortality for Cryptococcus gattii infection in dogs and cats of southwestern British Columbia. Can Vet J. 2006;47(10):993998.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30.

    Moore SA. Managing neuropathic pain in dogs. Front Vet Sci. 2016;3:12. doi:10.3389/fvets.2016.00012

  • 31.

    Levine GJ, Cook JR. Cerebrospinal fluid and central nervous system cytology. In: Cowell and Tyler’s Diagnostic Cytology and Hematology of the Dog and Cat. Elsevier; 2020:210228.

    • Search Google Scholar
    • Export Citation
  • 32.

    Wasserstein RL, Schirm AL, Lazar NA. Moving to a world beyond “p < 0.05.” Am Stat. 2019;73(suppl 1):119. doi:10.1080/00031305.2019.1583913

    • Search Google Scholar
    • Export Citation
  • 33.

    Lester SJ, Kowalewich NJ, Bartlett KH, Krockenberger MB, Fairfax TM, Malik R. Clinicopathologic features of an unusual outbreak of cryptococcosis in dogs, cats, ferrets, and a bird: 38 cases (January to July 2003). J Am Vet Med Assoc. 2004;225(11):17161722. doi:10.2460/javma.2004.225.1716

    • Search Google Scholar
    • Export Citation
  • 34.

    Medleau L, Marks MA, Brown J, Borges WL. Clinical evaluation of a cryptococcal antigen latex agglutination test for diagnosis of cryptococcosis in cats. J Am Vet Med Assoc. 1990;196(9):14701473.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 35.

    Malik R, Craig A, Wigney DI, Martin P, Love DN. Combination chemotherapy of canine and feline cryptococcosis using subcutaneously administered amphotericin B. Aust Vet J. 1996;73(4):124128. doi:10.1111/j.1751-0813.1996.tb10003.x

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 36.

    Jacobs GJ, Medleau L, Calvert C, Brown J. Cryptococcal infection in cats: factors influencing treatment outcome, and results of sequential serum antigen titers in 35 cats. J Vet Intern Med. 1997;11(1):14. doi:10.1111/j.1939-1676.1997.tb00064.x

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 37.

    Malik R, McPetrie R, Wigney DI, Craig AJ, Love DN. A latex cryptococcal antigen agglutination test for diagnosis and monitoring of therapy for cryptococcosis. Aust Vet J. 1996;74(5):358364. doi:10.1111/j.1751-0813.1996.tb15445.x

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 38.

    Perfect JR, Dismukes WE, Dromer F, et al. Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the Infectious Diseases Society of America. Clin Infect Dis. 2010;50(3):291322. doi:10.1086/649858

    • Search Google Scholar
    • Export Citation
  • 39.

    Trivedi SR, Malik R, Meyer W, Sykes JE. Feline cryptococcosis. J Feline Med Surg. 2011;13(3):163172. doi:10.1016/j.jfms.2011.01.009

  • 40.

    Malik R, Medeiros C, Wigney D, Love DN. Suspected drug eruption in seven dogs during administration of flucytosine. Aust Vet J. 1996;74(4):285288. doi:10.1111/j.1751-0813.1996.tb13776.x

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 41.

    Béguin J, Kohlhauer M, Laloy E, et al. Pharmacokinetics and tolerance of repeated oral administration of 5-fluorocytosine in healthy dogs. BMC Vet Res. 2021;17(1):220. doi:10.1186/s12917-021-02927-5

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 42.

    Wiebe V, Karriker M. Therapy of systemic fungal infections: a pharmacologic perspective. Clin Tech Small Anim Pract. 2005;20(4):250257. doi:10.1053/j.ctsap.2005.07.006

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 43.

    Skipper CP, Atukunda M, Stadelman A, et al. Phase I EnACT trial of the safety and tolerability of a novel oral formulation of amphotericin B. Antimicrob Agents Chemother. 2020;64(10):e00838-20. doi:10.1128/AAC.00838-20

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 44.

    Wasan KM, Wasan EK, Hnik P. Assessing the safety, tolerability, pharmacokinetics, and biodistribution of novel oral formulations of amphotericin b following single- and multiple-dose administration to Beagle dogs. Antimicrob Agents Chemother. 2020;64(11):e01111-20. doi:10.1128/AAC.01111-20

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 45.

    Tenforde MW, Shapiro AE, Rouse B, et al. Treatment for HIV-associated cryptococcal meningitis. Cochrane Database Syst Rev. 2018;7(7):CD005647. doi:10.1002/14651858.CD005647.pub3

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 46.

    Jarvis JN, Lawrence DS, Meya DB, et al. Single-dose liposomal amphotericin B treatment for cryptococcal meningitis. N Engl J Med. 2022;386(12):11091120. doi:10.1056/NEJMoa2111904

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 47.

    Graybill JR, Sobel J, Saag M, et al. Diagnosis and management of increased intracranial pressure in patients with AIDS and cryptococcal meningitis. Clin Infect Dis. 2000;30(1):4754. doi:10.1086/313603

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 48.

    Beardsley J, Wolbers M, Kibengo FM, et al. Adjunctive dexamethasone in HIV-associated cryptococcal meningitis. N Engl J Med. 2016;374(6):542554. doi:10.1056/NEJMoa1509024

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 49.

    McEwan SA, Sykes JE. Nasopharyngeal cryptococcosis in a cat: interlaboratory variation in cryptococcal antigen assay test results. JFMS Open Rep. 2022;8(1):20551169221074624. doi:10.1177/20551169221074624

    • Search Google Scholar
    • Export Citation

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